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Like insulin, leucine stimulates the mammalian target of rapamycin (mTOR)/p70 ribosomal $6 kinase ([p70.sup.S6K]) axis in various organs. Insulin proceeds via the canonical association of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent protein kinase-1 (PDK1), and protein kinase B (PKB/Akt). The signaling involved in leucine effect, although known to implicate a PI3K mechanism independent of PKB/Akt, is more poorly understood. In this study, we investigated whether PDK1 could also participate in the events leading to mTOR/[p70.sup.S6K] activation in response to leucine in the heart. In wild-type hearts, both leucine and insulin increased [p70.sup.S6K] activity whereas, in contrast to insulin, leucine was unable to activate PKB/Akt. The changes in [p70.sup.S6K] activity induced by insulin and leucine correlated with changes in phosphorylation of [Thr.sup.389], the mTOR phosphorylation site on [p70.sup.S6K], and of [Set.sup.2448] on mTOR, both related to mTOR activity. Leucine also triggered phosphorylation of the proline-rich Akt/PKB substrate of 40 kDa (PRAS40), a new pivotal mTOR regulator. In PDK1 knockout hearts, leucine, similarly to insulin, failed to induce the phosphorylation of mTOR and [p70.sup.S6K], leading to the absence of [p70.sup.S6K] activation. The loss of leucine effect in absence of PDK1 correlated with the lack of PRAS40 phosphorylation. Moreover, the introduction in PDK1 of the L155E mutation, which is known to preserve the insulin-induced and PKB/Akt-dependent phosphorylation of mTOR/[p70.sup.S6K], suppressed all leucine effects, including phosphorylation of mTOR, PRAS40, and [p70.sup.S6K]. We conclude that the leucine-induced stimulation of the cardiac PRAS40/mTOR/[p70.sup.S6K] pathway requires PDK1 in a way that differs from that of insulin. phosphoinositide-dependent protein kinase-1; mammalian target of rapamycin; proline-rich Akt/PKB substrate of 40 kDa; p70 ribosomal protein S6 kinase; amino acid; heart doi: 10.1152/ajpendo.00421.2009.

In 1963, Lancet published a paper by Randle et al. that proposed a 'glucose-fatty acid cycle' to describe fuel flux between and fuel selection by tissues. The original biochemical mechanism explained the inhibition of glucose oxidation by fatty acids. Since then, the principle has been confirmed by many investigators. At the same time, many new mechanisms controlling the utilization of glucose and fatty acids have been discovered. Here, we review the known short- and long-term mechanisms involved in the control of glucose and fatty acid utilization at the cytoplasmic and mitochondrial level in mammalian muscle and liver under normal and pathophysiological conditions. They include allosteric control, reversible phosphorylation, and the expression of key enzymes. However, the complexity is formidable. We suggest that not all chapters of the Randle cycle have been written. adenosine 5'-monophosphate-activated protein kinase; fatty acids; glucose; heart; insulin resistance; liver; mitochondria; peroxisome proliferator-activated receptor; skeletal muscle; type 2 diabetes

Several modular and numerical studies are conducted to explain the impact of an applied mechanical stress on the electroacoustic behavior in the integrated piezoelectric materials. The considered mode, azimuthal angle and the elevation angle are shown to highly affect the stress effects.

A novel formulation of the electrical input impedance of a single element transducer is discussed. Results suggest that the proposed model successfully deduces the efficiency of a transducer in emission mode and optimizes its characteristics for maximum radiated acoustical power.

In myogenic [C.sub.2][C.sub.12] cells, 5 mM creatine increased the incorporation of labeled [[sup.35]S]methionine into sarcoplasmic (+20%, P < 0.05) and myofibrillar proteins (+50%, P < 0.01). Creatine also promoted the fusion of myoblasts assessed by an increased number of nuclei incorporated within myotubes (+40%, P < 0.001). Expression of myosin heavy chain type II (+1,300%, P < 0.001), troponin T (+65%, P < 0.01), and titin (+40%, P < 0.05) was enhanced by creatine. Mannitol, taurine, and [beta]-alanine did not mimic the effect of creatine, ruling out an osmolarity-dependent mechanism. The addition of rapamycin, the inhibitor of mammalian target of rapamycin/70-kDa ribosomal $6 protein kinase (mTOR/[p70.sup.s6k]) pathway, and SB 202190, the inhibitor of p38, completely blocked differentiation in control cells, and creatine did not reverse this inhibition, suggesting that the mTOR/[p70.sup.s6k] and p38 pathways could be potentially involved in the effect induced by creatine on differentiation. Creatine upregulated phosphorylation of protein kinase B (Akt/PKB; +60%, P < 0.001), glycogen synthase kinase-3 (+70%, P < 0.001), and [p70.sup.s6k] (+50%, P < 0.001). Creatine also affected the phosphorylation state of p38 (-50% at 24 h and +70% at 96 h, P < 0.05) as well as the nuclear content of its downstream targets myocyte enhancer factor-2 (-55% at 48 h and +170% at 96 h, P < 0.05) and MyoD (+60%, P < 0.01). In conclusion, this study points out the involvement of the p38 and the Akt/[PKB-p70.sup.s6k] pathways in the enhanced differentiation induced by creatine in [C.sub.2][C.sub.12] cells. protein synthesis; insulin-like growth factor; mitogen-activated protein kinase; extracellular signal-regulated kinase 1/2; 70-kDa ribosomal $6 protein kinase

AMP-activated protein kinase (AMPK) is a major sensor and regulator of the energetic state of the cell. Little is known about the specific role of AMPK[[alpha].sub.2], the major AMPK isoform in the heart, in response to global ischemia. We used AMPKc~2-knockout ([AMPK[[alpha].sub.2].sup.-/-] ) mice to evaluate the consequences of AMPK[[alpha].sub.2] deletion during normoxia and ischemia, with glucose as the sole substrate. Hemodynamic measurements from echocardiography of hearts from AMPK[[[alpha].sub.2].sup.-/-] mice during normoxia showed no significant modification compared with wild-type animals. In contrast, the response of hearts from AMPK[[[alpha].sub.2].sup.-/-] mice to no-flow ischemia was characterized by a more rapid onset of ischemia-induced contracture. This ischemic contracture was associated with a decrease in ATP content, lactate production, glycogen content, and AMPK[[beta].sub.2] content. Hearts from AMPK[[[alpha].sub.2].sup.-/-]mice were also characterized by a decreased phosphorylation state of acetyl-CoA carboxylase during normoxia and ischemia. Despite an apparent worse metabolic adaptation during ischemia, the absence of AMPK[[alpha].sub.2] does not exacerbate impairment of the recovery of postischemic contractile function. In conclusion, AMPK[[alpha].sub.2] is required for the metabolic response of the heart to no-flow ischemia. The remaining AMPK[[alpha].sub.1] cannot compensate for the absence of AMPK[[alpha].sub.2]. glycogen; glycolysis; acetyl-CoA carboxylase

A screen-printed PZT thick film with a final thickness of about 40 [mu]m was deposited on a porous PZT substrate to obtain an integrated structure for ultrasonic transducer applications, effectively decreasing the number of steps in the fabrication of high-frequency, single-element transducers. The porous PZT substrates allow high acoustic impedance and attenuation to be obtained, satisfying transducer backing requirements for medical imaging, resulting in good sensitivity and axial resolution.

Diabetic hearts are known to be more susceptible to ischemic disease. Biguanides, like metformin, are known antidiabetic drugs that lower blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in muscle. Part of these metabolic effects is thought to be mediated by the activation of AMP-activated protein kinase (AMPK). In this work, we studied the relationship between AMPK activation and glucose uptake stimulation by biguanides and oligomycin, another AMPK activator, in both insulin-sensitive and insulin-resistant cardiomyocytes. In insulin-sensitive cardiomyocytes, insulin, biguanides and oligomycin were able to stimulate glucose uptake with the same efficiency. Stimulation of glucose uptake by insulin or biguanides was correlated to protein kinase B (PKB) or AMPK activation, respectively, and were additive. In insulin-resistant cardiomyocytes, where insulin stimulation of glucose uptake was greatly reduced, biguanides or oligomycin, in the absence of insulin, induced a higher stimulation of glucose uptake than that obtained in insulin-sensitive cells. This stimulation was correlated with the activation of both AMPK and PKB and was sensitive to the phosphatidylinositol-3-kinase/PKB pathway inhibitors. Finally, an adenoviral-mediated expression of a constitutively active form of AMPK increased both PKB phosphorylation and glucose uptake in insulin-resistant cardiomyocytes. We concluded that AMPK activators, like biguanides and oligomycin, are able to restore glucose uptake stimulation, in the absence of insulin, in insulin-resistant cardiomyocytes via the additive activation of AMPK and PKB. Our results suggest that AMPK activation could restore normal glucose metabolism in diabetic hearts and could be a potential therapeutic approach to treat insulin resistance. diabetes; AMP-activated protein kinase; mefformin; oligomycin

Author(s): Serge Clément [1, 2]; Ulrike Krause [2, 3]; Florence Desmedt [4]; Jean-François Tanti [5]; Jens Behrends [1]; Xavier Pesesse [4]; Takehiko Sasaki [6]; Joseph Penninger [6]; Margaret Doherty [7]; [...]

Some ferroelectric particles seem to be in contact in a high volume fraction particle-loaded piezocomposite as in a 3-3 connectivity material. Others are isolated in the polymer matrix, as in a pure 0-3 connectivity material. Such a material can be considered as a composite of composites characterized by a 3-3(03) connectivity. Two others have described a matrix method to compute all of the effective parameters of pure 0-3 and 3-3 connectivity piezocomposites. These previous models were employed to determine the effective characteristics of 3-3(0-3) composite.

The effects of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), a guanosine 3',5'-cyclic monophosphate (cGMP) analog, on regulatory steps of glucose metabolism in isolated working rat hearts perfused with glucose as the substrate were examined. Findings revealed that restriction of glucose uptake by S-nitroso-N-acetylpenicillamine or 8-BrcGMP reduced heart work. This was reversed by adding alternative oxidizable substrates together with glucose.